Fig. 1: BET inhibition represses adaptive RTK expression following BRAF/MEK inhibitors treatment in BRAF-mutant melanoma.

a RPPA analysis for the BRAF-mutant human melanoma cell lines, A375, 1205Lu, and M238, after 24âh of treatment with BRAFi/MEKi (dabrafenib, 50ânM + trametinib, 5ânM). RPPA scores for proteins involved in RTK signalling that were statistically significant (pâ<â0.05) with BRAFi/MEKi versus vehicle (DMSO) treatment samples. b Western blots for RPPA-identified proteins in a after treatment with BRAFi/MEKi over a 24-h time course. c RPPA analysis for the cell lines, A375, 1205Lu, and M238, after 24âh of treatment with BRAFi/MEKi (dabrafenib, 50ânM + trametinib, 5ânM) Âħ BETi in a dose-dependent manner (either JQ1: 0.01, 0.1, 1, and 5âÎĵM or PLX51107: 1, 2, and 4âÎĵM). Shown are antibodies for proteins involved in RTK signalling found to be statistically significant (pâ<â0.05) in at least one comparison between BRAFi/MEKiâÂħâBETi-treated groups. d Representative Western blots of three (nâ=â3) independent experiments for RTK proteins after 24âh of combination treatment with BRAFi/MEKi Âħ BETi in a dose-dependent manner for the doses described above.